TY - JOUR
T1 - A comparison of brain magnetic resonance imaging lesions in multiple sclerosis by race with reference to disability progression
AU - Nakamura, Yuri
AU - Gaetano, Laura
AU - Matsushita, Takuya
AU - Anna, Altermatt
AU - Sprenger, Till
AU - Radue, Ernst Wilhelm
AU - Wuerfel, Jens
AU - Bauer, Lorena
AU - Amann, Michael
AU - Shinoda, Koji
AU - Isobe, Noriko
AU - Yamasaki, Ryo
AU - Saida, Takahiko
AU - Kappos, Ludwig
AU - Kira, Jun ichi
N1 - Funding Information:
YN, AA, LB, and MA declare that they have no competing interests. LG reports personal fees from Novartis AG. TM received a grant and payment from Bayer Schering Pharma and Takeda Pharmaceutical Company for manuscript preparation and for development of educational presentations, and also received speaker honoraria payments from Mitsubishi Tanabe Pharma, Bayer Schering Pharma, and Biogen Idec Japan. Till S received previous and/or current payments for consulting, speaking activities (Actelion, Biogen Idec, Electrocore, Sanofi Genzyme, Mitsubishi Pharma, Teva, Novartis), and grants (EFIC-Grünenthal, Novartis Pharmaceuticals Switzerland, Swiss MS Society, Swiss National Research Foundation). EWR received speaker honoraria and travel compensation from Bayer Schering, Biogen, Fondazione Italiana Sclerosi Multipla, Genzyme, Novartis, Merck Serono, MorphoSys, and Synthon; consulted for Bayer Schering, Biogen Idec, Fondazione Italiana Sclerosi Multipla, Genzyme, Novartis, Merck Serono, Synthon, and MorphoSys; and received institutional research support from Novartis, Biogen Idec, Actelion, Basilea, SAKK, and Synarc. JW is CEO of MIAC AG. He served on scientific advisory board for Actelion, Genzyme, Novartis, Teva, and Roche; he received travel support and/or speaker honoraria from Bayer, Biogen, and Novartis; he received research support from the EU (Horizon2020), the German Ministry of Education and Research and the German Ministry of Economy. KS has received grants from the Japan Intractable Disease Research Foundation, Japanese Multiple Sclerosis Society, and the Japan Society for the Promotion of Science; and received personal fees from Takeda Pharmaceutical Company and Biogen Japan. NI has received grants and personal fees from Tanabe Mitsubishi Pharma, Bayer Yakuhin, Ltd., and Japan Blood Products Organization. RY has received grants from the Japan Society for the Promotion of Science, Bayer Schering Pharma, Biogen Idec Japan, Novartis Pharma, and Mitsubishi Tanabe Pharma; and received research support from the Ministry of Education, Culture, Sports, Science and Technology of Japan and the Ministry of Health, Labour, and Welfare, Japan. Takahiko S has received funding from, held board membership of, spoken at scientific meetings for, prepared manuscripts for, and had consulting agreements with Astellas Pharma, Bayer Schering, Biogen Japan, Daiichi Sankyo, Eisai, Kaketsuken, Merck Serono, Mitsubishi Tanabe Pharma, Nihon Pharmaceutical, Novartis Pharma, Ono Pharmaceutical, Sanofi, TDS Japan, and Teijin. LK’s Institution (University Hospital Basel) received exclusive research support at the Department of Neurology, including steering committee, advisory board, and consultancy fees from Actelion, Alkermes, Almirall, Bayer, Biogen, df-mp, Excemed, GeNeuro SA, Genzyme, Merck, Mitsubishi Pharma, Novartis, Receptos, Roche, Sanofi-Aventis, Santhera, Teva, and Vianex, and royalties from Neurostatus products. For educational activities of the Department, the institution received honoraria from Allergan, Almirall, Bayer, Biogen, Excemed, Genzyme, Merck, Novartis, Pfizer, Sanofi-Aventis, Teva, and UCB. LK has served as principal investigator for the following drug studies: BOLD EXT, EXPAND (BAF312, Novartis), DECIDE, DECIDE EXT (Daclizumab HYP, Biogen), ENDORSE (BG00012, Biogen), FINGORETT, FTYUMBRELLA, INFORMS, INFORMS EXT LONGTERM (Fingolimod, Novartis), MOMENTUM (Amiselimod, Mitsubishi) OCRELIZUMAB PHASE II EXT, OPERA, ORATORIO (Ocrelizumab, Roche), REFLEXION (IFN β-1a, Merck), STRATA EXT (Natalizumab, Biogen Idec), and TERIFLUNOMIDE EXT (Teriflunomide, Sanofi-Aventis). Research at the MS center in Basel was supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, the European Union, and Roche Research Foundations. The institution has also received grants for patient services from Bayer, Merck, and Teva. JK has received grants from the Ministry of Health, Labour, and Welfare, Japan, the Ministry of Education, Culture, Sports, Science and Technology of Japan, the Japan Society for the Promotion of Science, the Japan Agency for Medical Research and Development, AMED, Japan; and received grants and personal fees from Biogen Idec Japan, Bayer Healthcare, Novartis Pharma, and Mitsubishi Tanabe Pharma, Eisai, Sanofi, Nobelpharma, Otsuka Pharmaceutical, Chugai Pharmaceutical Company, and Teijin Pharma. This independent academic research was supported by Novartis Pharma A.G., Novartis Pharma K.K., and Mitsubishi Tanabe Pharma Corporation, who provided baseline demographic data for the patients analyzed. Novartis and Mitsubishi Tanabe Pharma Corporation played no role in the design, methods, data management, or analysis of the study, or in the decision to publish.
Funding Information:
This study was supported in part by a Health and Labour Sciences Research Grant on Intractable Diseases (H29-Nanchitou (Nan)-Ippan-043) from the Ministry of Health, Labour, and Welfare, Japan, by the “Practical Research Project for Rare/Intractable Diseases” from the Japan Agency for Medical Research and Development, AMED, Japan, by a research grant from the Japanese Multiple Sclerosis Society, by a research grant from the Japan Intractable Disease Research Foundation, by ‘Glial Assembly’ Grants-in-Aid for Scientific Research on Innovative Areas (MEXT KAKENHI Grant Number 25117012) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, by a Grant-in-Aid for Scientific Research (A) (JSPS KAKENHI Grant Number 16H02657), by a Grant-in-Aid for Scientific Research (C) (JSPS KAKENHI Grant Numbers 16 K09694), by a Grant-in-Aid for Scientific Research (C) (JSPS KAKENHI Grant Number 15 K09341), and by a Grant-in-Aid for Young Scientists (B) (JSPS KAKENHI Grant Number 17 K16125) from the Japan Society for the Promotion of Science, Japan. None of the funding bodies played any role in the study design, data collection and analysis, data interpretation, or writing of the manuscript.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/9/5
Y1 - 2018/9/5
N2 - Background: We compared the magnetic resonance imaging (MRI) features between Japanese and Caucasian patients with multiple sclerosis (MS), and identified the relationships between MRI features and disability. Methods: From the baseline data of phase II fingolimod trials, 95 Japanese and 246 Caucasian relapsing-remitting MS patients were enrolled. The number, volume, and distribution of brain MRI lesions were evaluated using T2-weighted (T2W) images. Cross-sectional total normalized brain volume (NBV), normalized cortical gray matter volume, normalized deep gray matter volume (NDGMV), normalized white matter volume (NWMV), and normalized thalamic volume were measured. Results: Japanese patients had significantly lower Expanded Disability Status Scale (EDSS) scores than Caucasian patients (mean 2.0 vs. 2.3, p = 0.008), despite a similar disease duration. Japanese patients showed a trend towards fewer T2W-lesions (median 50 vs. 65, p = 0.08) and significantly lower frequencies of cerebellar and parietal lobe lesions (p = 0.02 for both) than Caucasian patients. There were no differences in T2W-lesion volume between races, whereas Japanese patients had a significantly larger T2W-lesion volume per lesion compared with Caucasian patients (median 140 mm3 vs. 85 mm3, p < 0.0001). T2W-lesion volumes were positively correlated with EDSS scores in Japanese patients (p < 0.0001). In both races, NBV, normalized cortical gray matter volume, NDGMV, and thalamic volume were negatively correlated with disease duration and EDSS scores (p < 0.01 for all). NWMV was negatively correlated with disease duration and EDSS scores only in Caucasian patients (p = 0.03 and p = 0.004, respectively). NBV, NDGMV, NWMV, and thalamic volume were consistently smaller in Japanese compared with Caucasian patients throughout the entire examined disease duration (p = 0.046, p = 0.01, p = 0.005, and p = 0.04, respectively). Japanese patients had a significantly faster reduction in NDGMV (p = 0.001), particularly for thalamic volume (p = 0.001), with disease duration compared with Caucasian patients. Conclusions: Gray matter atrophy is a common denominator for disability in Japanese and Caucasian patients. Additional contributory factors for disability include T2W-lesion volume in Japanese patients and white matter atrophy in Caucasian patients. Less frequent parietal and cerebellar involvement with fewer T2W-lesions may underlie milder disability in Japanese patients.
AB - Background: We compared the magnetic resonance imaging (MRI) features between Japanese and Caucasian patients with multiple sclerosis (MS), and identified the relationships between MRI features and disability. Methods: From the baseline data of phase II fingolimod trials, 95 Japanese and 246 Caucasian relapsing-remitting MS patients were enrolled. The number, volume, and distribution of brain MRI lesions were evaluated using T2-weighted (T2W) images. Cross-sectional total normalized brain volume (NBV), normalized cortical gray matter volume, normalized deep gray matter volume (NDGMV), normalized white matter volume (NWMV), and normalized thalamic volume were measured. Results: Japanese patients had significantly lower Expanded Disability Status Scale (EDSS) scores than Caucasian patients (mean 2.0 vs. 2.3, p = 0.008), despite a similar disease duration. Japanese patients showed a trend towards fewer T2W-lesions (median 50 vs. 65, p = 0.08) and significantly lower frequencies of cerebellar and parietal lobe lesions (p = 0.02 for both) than Caucasian patients. There were no differences in T2W-lesion volume between races, whereas Japanese patients had a significantly larger T2W-lesion volume per lesion compared with Caucasian patients (median 140 mm3 vs. 85 mm3, p < 0.0001). T2W-lesion volumes were positively correlated with EDSS scores in Japanese patients (p < 0.0001). In both races, NBV, normalized cortical gray matter volume, NDGMV, and thalamic volume were negatively correlated with disease duration and EDSS scores (p < 0.01 for all). NWMV was negatively correlated with disease duration and EDSS scores only in Caucasian patients (p = 0.03 and p = 0.004, respectively). NBV, NDGMV, NWMV, and thalamic volume were consistently smaller in Japanese compared with Caucasian patients throughout the entire examined disease duration (p = 0.046, p = 0.01, p = 0.005, and p = 0.04, respectively). Japanese patients had a significantly faster reduction in NDGMV (p = 0.001), particularly for thalamic volume (p = 0.001), with disease duration compared with Caucasian patients. Conclusions: Gray matter atrophy is a common denominator for disability in Japanese and Caucasian patients. Additional contributory factors for disability include T2W-lesion volume in Japanese patients and white matter atrophy in Caucasian patients. Less frequent parietal and cerebellar involvement with fewer T2W-lesions may underlie milder disability in Japanese patients.
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U2 - 10.1186/s12974-018-1295-1
DO - 10.1186/s12974-018-1295-1
M3 - Article
C2 - 30185189
AN - SCOPUS:85052954134
VL - 15
JO - Journal of Neuroinflammation
JF - Journal of Neuroinflammation
SN - 1742-2094
IS - 1
M1 - 255
ER -